This Midcareer Investigator Award application seeks support to provide Dr. Matthew Smith with protected time to devote to patient-oriented research and to act as an effective research mentor for clinical fellows and junior faculty. The candidate is the Clinical Research Director in Genitourinary Oncology at Massachusetts General Hospital and Co-Director of the Clinical Research in Genitourinary Malignancies for Dana-Farber Harvard Cancer Center (DF/HCC). His clinical research program focuses on cancer survivorship, prevention and treatment of bone metastases, and novel therapies for advanced prostate cancer. He has a strong record of patient-oriented research, independent peer-reviewed funding, and successful mentoring. The timing of this application coincides with the new directions in the candidate's patient-oriented research program, additional successful grant applications, recent selection of a new trainee, and the planned expansion of mentoring activities. The broad long-term objective of this application is to advance both the patient-oriented research program and mentoring activities of the candidate. The Specific Aims are: 1. To decrease disease and treatment-related morbidity in cancer survivors, to treat and prevent bone metastases, and to develop novel therapies for advanced prostate cancer. 2. To evaluate mechanism(s) of treatment-related diabetes and cardiovascular disease in prostate cancer survivors, a new direction in the candidate's patient-oriented research program. 3. To mentor new investigators in patient-oriented research. This research program may advance public health by developing new strategies to treat prostate cancer and to prevent bone metastases, a major cause of prostate cancer morbidity. In addition, this research program may help decrease the burden of cancer treatment for prostate cancer survivors.